Why should I test for FTD?

Knowing whether FTD has a genetic cause can help explain what the disease course may look like over time, clarify who else in the family may be at risk, and open doors to clinical trials that focus on specific genes.

What kind of genetic test should I get for FTD?

There are several types of genetic tests: single-gene testing (focuses on one specific gene), gene panels (test a selected group of genes), whole exome sequencing (WES, looks at protein-coding parts of all genes), and whole genome sequencing (WGS, sequences all of your DNA). The right choice depends on your family history, what answers you're hoping to find, and whether testing is for medical care, family planning, or research.

How can I get genetic testing for FTD?

Talk to a genetic counselor who can discuss the pros and cons of different genetic testing options, possible test outcomes, what results could mean for family members, and the emotional side of testing. A genetic counselor can help facilitate your testing and meet with you when results are ready to walk you through them.

What Is Progranulin? Understanding Its Role in GRN-Related Frontotemporal Degeneration

If you or someone in your family has been diagnosed with Frontotemporal Degeneration (FTD), you may be looking for answers about what causes the disease and what researchers are doing to develop treatments.

One cause of FTD involves changes in a gene called GRN, which affects the amount of a protein called progranulin in the brain. This blog explains what progranulin does, how genetic changes can reduce progranulin levels, and how scientists are working to develop treatments that target this pathway.

What is progranulin?

Progranulin is a protein made by a gene called GRN. It is found throughout the body, including in the brain.

In the brain, progranulin is produced by several types of cells, including:

Neurons, which send signals that allow us to think, speak, and move
Microglia, which are the brain’s immune cells, that help protect the brain and respond to injury

Scientists believe progranulin plays several important roles in keeping brain cells healthy.

Progranulin helps the brain in several ways:

1. Supporting brain cell health
Progranulin helps brain cells survive and function properly.

2. Regulating inflammation
The brain has its own immune system. Progranulin helps keep this system balanced so that inflammation does not become harmful.

3. Helping cells remove waste
Cells constantly break down and recycle old or damaged materials. Progranulin helps support structures inside cells called lysosomes, which act like recycling centers.

4. Helping the brain respond to injury
Progranulin may also help support tissue repair after damage or stress.

Together, these roles help maintain the health and stability of brain cells over time.

What happens when there is a change in the GRN gene?

Some people inherit a genetic change (sometimes called a variant or mutation) in the GRN gene.

Most GRN-related changes cause the body to produce about half the normal amount of progranulin. Scientists call this progranulin deficiency, also termed progranulin haploinsufficiency.

When progranulin levels are too low:

Brain cells may not manage inflammation properly
Cellular recycling systems may not work as efficiently
Certain proteins can build up in brain cells

Over time, these changes can damage brain cells, especially in the frontal and temporal lobes of the brain.

This damage can lead to GRN-related FTD, a genetic form of frontotemporal degeneration.

What symptoms can occur in GRN-related FTD?

Symptoms often begin in mid-adulthood, although the exact age can vary widely—even within the same family.

Common symptoms may include:

Changes in behavior or personality
Difficulty with planning or decision-making
Loss of empathy or social awareness
Language problems, such as trouble finding words or understanding speech

Because these symptoms develop slowly over time, they are sometimes mistaken for other conditions at first.

How do I know if I carry a GRN gene change?

If you've been diagnosed with FTD, you may want to consider genetic counseling.

A genetic counselor can help you:

Review your personal and family medical history
Understand whether genetic testing may be helpful
Discuss the benefits, limitations, and possible results of testing
Support you in making decisions that feel right for you

If you decide to move forward, genetic testing usually involves a simple blood or saliva test and a genetic counselor will meet with you to discuss what the results mean for you and your family members.

If you are interested in genetic counseling and/or genetic testing, the Progranulin Information Navigator offers free genetic counseling and testing for individuals diagnosed with FTD, as well as family members of individuals who are known to carry a progranulin (GRN) gene variant.

You can find out if you are eligible at: https://www.progranulinnavigator.org/genetic-testing-screener

What treatment approaches are researchers exploring?

Currently, there is no cure for GRN-related FTD. However, many researchers and biotech companies are working to develop treatments that target progranulin biology.

Several approaches to increase progranulin levels are being studied in clinical trials. Clinical trials are a specific type of medical research that test whether a new experimental medicine or treatment works well and is safe. The goal of clinical trials for GRN-related FTD is to restore progranulin closer to normal levels to help support brain cell health.

1. Gene replacement

Gene therapy delivers a working copy of the GRN gene to brain cells, where the cell uses it to make more progranulin protein.

2. Protein replacement

Protein replacement delivers progranulin protein to the brain, where it can be taken up and used by cells.

3. Blocking sortilin binding

Sortilin is a protein that helps regulate how progranulin is recycled in the brain. When progranulin binds to sortilin, the progranulin is pulled into cells and broken down. If this binding is blocked, more progranulin can remain available in the brain.

How can I learn about clinical trials?

Clinical trials help researchers understand whether new treatments are safe and effective.

If you or a family member has a GRN gene change known to cause FTD, you may want to explore whether a clinical trial could be an option.

You can search for active studies at: https://www.progranulinnavigator.org/directory

Participation in research is always voluntary, while we don’t know whether experimental treatments will have a positive effect (or possibly be harmful), many individuals choose to participate with the hope of slowing disease progression and a desire to advance scientific understanding and future treatments.

Learn more

You may also find these resources helpful:

www.aftd.org
https://www.bluefieldproject.org
https://www.curegrn.org
Our other blog posts on FTD and genetic testing

References

Townley RA, Boeve BF, Benarroch EE. Progranulin: Functions and neurologic correlations. Neurology. 2018.

Rhinn H et al. Progranulin as a therapeutic target in neurodegenerative diseases. Trends in Pharmacological Sciences. 2022.

NOTE: The Site is provided for informational purposes only, and is not intended to provide, or be a substitute for, medical advice, diagnosis or treatment recommendations. Any user that intends to use information from the Site should first consult with their healthcare provider.